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Acetylation of Tat Defines a CyclinT1-Independent Step in HIV Transactivation

机译:Tat的乙酰化定义了HIV转录激活的CyclinT1独立步骤

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摘要

The HIV transcriptional activator Tat is acetylated by p300 at a single lysine residue in the TAR RNA binding domain. We have generated monoclonal and polyclonal antibodies specific for the acetylated form of Tat (AcTat). Microinjection of anti-AcTat antibodies inhibited Tat-mediated transactivation in cells. Similarly, the p300 inhibitor Lys-CoA and siRNA specific for p300 suppressed Tat transcriptional activity. Fulllength synthetic AcTat bound to TAR RNA with the same affinity as unacetylated Tat, but formation of a Tat-TAR-CyclinT1 ternary complex was completely inhibited in the presence of AcTat. We propose that Tat acetylation may help in dissociating the Tat cofactor CyclinT1 from TAR RNA and serve to transfer Tat onto the elongating RNA polymerase II.
机译:HIV转录激活因子Tat在TAR RNA结合结构域的单个赖氨酸残基处被p300乙酰化。我们已经生成了对Tat(AcTat)乙酰化形式具有特异性的单克隆和多克隆抗体。显微注射抗AcTat抗体可抑制细胞中Tat介导的反式激活。同样,p300抑制剂Lys-CoA和对p300特异的siRNA抑制Tat转录活性。全长合成AcTat以与未乙酰化Tat相同的亲和力与TAR RNA结合,但是在AcTat存在下,Tat-TAR-CyclinT1三元复合物的形成被完全抑制。我们提出,Tat乙酰化可能有助于从TAR RNA解离Tat辅助因子CyclinT1,并有助于将Tat转移到延长RNA聚合酶II上。

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